Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β

Martínez-Cingolani, Carolina; Grandclaudon, Maximilien; Jeanmougin, M.; Jouve, Mabel; Zollinger, Raphaël; Soumelis, Vassili

doi:10.1182/blood-2014-04-568311

Cited by 66 publications

(70 citation statements)

References 49 publications

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“…This probably explains why Milne et al (32) stated that monocyte differentiation with GM-CSF and TGF-b1 or BMP-7 but in the presence of serum was not a leading mechanism for LC-like cell generation. Conversely, two recent studies proposed that blood CD1c + DCs represent the most potent short-term LC precursors in humans (31,32). In this study, we brought strong evidence that monocytes can display a similar ability in a serumfree setting.…”

Section: Discussionsupporting

confidence: 51%

“…1C) (39). To compare classical monocytes with CD1c + blood DCs, which were recently shown to exhibit a high differentiation potential toward LC-like cells (31,32), both cell types were sorted from blood of healthy donors and differentiated with GM-CSF and TGF-b1 in 2% HSA for 7 d. A flow cytometric analysis of their respective CD1a and langerin expression showed similar abilities to differentiate into langerin high CD1a high cells (R3 gate; Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…We assumed that other serum lipids such as high-density lipoproteins might be able to act similarly. Thus, serum lipids appeared to be responsible for a marked alteration of LC differentiation of monocytes in previous studies (28,31,32).…”

Section: Serum Lipids Impair Lc Differentiation Of Monocytes With Tgfmentioning

confidence: 99%

“…Purity of sorted CD1 + DCs was assessed by flow cytometry and always achieved high yields (.98%; anti-human CD1c, clone L161, BioLegend, San Diego, CA). CD1 + DCs were then differentiated similarly to monocytes to obtain LClike cells resembling those described by Martínez-Cingolani et al (31) or Milne et al (32). When required, MDDCs and MDLCs were matured with 100 ng/ml Escherichia coli K-12 strain LPS and 1 mg/ml R848 (Cayla/ InvivoGen, Toulouse, France) for 24 h. Fifty to 80% pure skin LCs were isolated from skin surgical pieces as already described (33).…”

Section: Cells and Reagentsmentioning

confidence: 99%

See 3 more Smart Citations

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Picarda

Chéneau

Humbert

et al. 2016

The Journal of Immunology

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Langerhans cells (LCs) are epithelial APCs that sense danger signals and in turn trigger specific immune responses. In steady-state, they participate in the maintenance of peripheral tolerance to self-antigens whereas under inflammation LCs efficiently trigger immune responses in secondary lymphoid organs. It has been demonstrated in mice that LC-deprived epithelia are rapidly replenished by short half-life langerin-expressing monocyte-derived LCs (MDLCs). These surrogate LCs are thought to be progressively replaced by langerinhigh LCs arising from self-renewing epithelial precursors of hematopoietic origin. How LCs arise from blood monocytes is not fully understood. Hence, we sought to characterize key factors that induce differentiation of langerinhigh-expressing monocyte-derived Langerhans-like cells. We identified GM-CSF and TGF-β1 as key cytokines to generate langerinhigh-expressing cells but only in serum-free conditions. These cells were shown to express the LC-specific TROP-2 and Axl surface markers and contained Birbeck granules. Surprisingly, E-cadherin was not spontaneously expressed by these cells but required a direct contact with keratinocytes to be stably induced. MDLCs induced stronger allogeneic T cell proliferations but released low amounts of inflammatory cytokines upon TLR stimulation compared with donor-paired monocyte-derived dendritic cells. Immature langerinhigh MDLCs were responsive to MIP-3β/CCL20 and CTAC/CCL27 chemokine stimulations. Finally, we demonstrated that those cells behaved as bona fide LCs when inserted in a three-dimensional rebuilt epithelium by becoming activated upon TLR or UV light stimulations. Collectively, these results prompt us to propose these langerinhigh MDLCs as a relevant model to address LC biology–related questions.

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Section: Discussionsupporting

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Serum Lipids Impair Lc Differentiation Of Monocytes With Tgfmentioning

confidence: 99%

Section: Cells and Reagentsmentioning

confidence: 99%

See 2 more Smart Citations

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Picarda

Chéneau

Humbert

et al. 2016

The Journal of Immunology

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“…13 16 and readily acquire a Langerhans cell-like phenotype in vitro. 17,18 The differentiation potentials of monocytes and blood DCs overlap, and monocyte-derived DCs bear many markers in common with CD1c 1 myeloid DCs. 19 Monocytes have plasticity in many directions including DC and macrophage axes 20,21 and may also express langerin in vitro under certain conditions.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Milne

Bigley

Bacon

et al. 2017

Blood

159

132

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Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAPK pathway genes. BRAF V600E mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific polymerase chain reaction was used to map the neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAF V600E was tracked to classical monocytes, nonclassical monocytes, and CD1c 1 myeloid dendritic cells (DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors in the bone marrow of 4 patients. The pattern of involvement of peripheral blood myeloid cells was indistinguishable between LCH and ECD, although the histiocytic disorders were distinct to HCL. As reported in children, detection of BRAF V600E in peripheral blood of adults was a marker of active multisystem LCH. The healthy counterparts of myeloid cells affected by BRAF mutation had a range of differentiation potentials depending on exogenous signals. CD1c 1 DCs acquired high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and transforming growth factor b alone, whereas CD14 1 classical monocytes required additional notch ligation. Both classical and nonclassical monocytes, but not CD1c 1 DCs, made foamy macrophages easily in vitro with macrophage colony-stimulating factor and human serum. These studies are consistent with a hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD. (Blood. 2017;130(2):167-175)

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Langerhans cells and skin immune diseases

Zhu,

Yao,

2024

Eur J Immunol

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Langerhans cells (LCs) are the key antigen‐presenting cells in the epidermis in normal conditions and respond differentially to environmental and/or endogenous stimuli, exerting either proinflammatory or anti‐inflammatory effects. Current knowledge about LCs mainly originates from studies utilizing mouse models, whereas with the development of single‐cell techniques, there has been significant progress for human LCs, which has updated our understanding of the phenotype, ontogeny, differentiation regulation, and function of LCs. In this review, we delineated the progress of human LCs and summarized LCs’ function in inflammatory skin diseases, providing new ideas for precise regulation of LC function in the prevention and treatment of skin diseases.

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Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β

Abstract: Key Points Human blood BDCA-1+ DCs have precursor potential. TSLP can be implicated in LC ontogenesis during inflammation.

Cited by 66 publications

References 49 publications

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults

Langerhans cells and skin immune diseases

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